Skeletal muscle is one of the largest components at the tissue-system level of body composition and is involved in many biological processes. Weakness and frailty in the elderly, osteoporosis, and the cachexia of acquired immunodeficiency syndrome are only a few of the conditions in which muscle plays an important role. Despite the relevance of skeletal muscle to so many acute and chronic conditions, the methods used to estimate muscle in vivo remain limited and understudied. Accumulating evidence strongly suggests that most presently available methods of measuring muscle mass are inaccurate in general or systematically in error when applied to selected groups. The sources of error/bias may include: 1. a failure to account for changes in muscle composition that occur with aging (e.g., decreasing muscle contents of potassium and creatine-phosphate, relative expansion of extracellular fluid, changing fiber-type proportions, and intramuscular adipose tissue deposition); and 2. inadequate adjustment of models/methods for ethnicity (e.g., white-black differences in fiber-type proportions and muscle distribution). A major advance in the study of skeletal muscle in vivo was the introduction of whole-body computerized tomography (CT) and more recently magnetic resonance (MR) imaging. Pilot studies from our laboratory based on CT and other methods demonstrate inaccuracies and large systematic errors in most of the widely used methods for measuring muscle mass in vivo (e.g., neutron activation and CT muscle estimates (X plus/minus SD), 27.5 plus/minus 8.4 kg & 34.4 plus/minus 6.2 kg) differed by an average of 20.0% in healthy men; and anthropometric arm muscle area measurements in elderly women failed to detect significant (p<0.05) reductions in muscle mass. The overall aim of the proposed research program is twofold: to study, using state-of-the-art methods (e.g., MR imaging and spectroscopy, analyses of muscle biopsies, 13C-creatinine kinetics, & genetic markers of racial admixture) the biology (composition, distribution, and function) of skeletal muscle across age, gender, and ethnic groups, and to apply this information to the development of methods that will allow a broad range of investigators to estimate and appropriately interpret whole-body skeletal muscle mass in settings that range from epidemiologic field stations to the research laboratory. The hypotheses will be tested and specific aims carried out in 240 healthy white and black men and women over the age of 18 yrs. This research will fill an important gap in body composition methodology and provide extensive new information on the ethnic-specific changes that occur in muscle with aging.